Advanced bronchogenic carcinoma, colorectal carcinoma, breast carcinoma, and neuroblastoma account for a significant number of deaths per year from cancer in the United States. A recent advance which would allow the correct choice of chemotherapy for an individual patient with one of these malignancies has been the development of the human tumor stem cell assay by Hamburger and Salmon (1). However, at the present time the assay has several problems which must be solved before the system can be used for widespread patient care applications. One major problem is that with the present methodology it takes 21 days for colonies to grow before they can be counted and sensitivity to chemotherapy determined. This 3 week delay is too long to wait before starting an anticancer agent in most clinical situations. A second major problem is that the assay system consumes such a large amount of technical time for counting colonies (10 hours per tumor specimen) that the assay system is not practical even for institutions with reasonable technical support. The first phase of this research proposal addresses these two problems by developing a technique that will provide an early answer (6 days or less) as to the number of colonies which survive in vitro drug treatment. This would give the clinician an early indication of drug sensitivity of the tumor. This radiolabeling technique would also obviate the need for colony counting which would meand a great savings of time. This radiolabeling technique could also provide a powerful tool for studying the kinetics, metabolism, drug transport and resistance of human tumor stem cells through the use of a variety of labeled proteins and drugs. The second phase of this proposal stresses the utilization of the radiolabeling technique (developed in phase I) to study the growth kinetics of the human tumor stem cell. It is hoped that these studies of what is potentially the proliferating compartment of the tumor will lead to a better understanding of the tumor kinetics and design of clinical trials to exploit this understanding for treatment purposes.